rs713503

Variant names:

• chr11-16978335-A-C
• rs713503
• NM_001329630.2:c.221+35654T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001329630.2(PLEKHA7):​c.221+35654T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,012 control chromosomes in the GnomAD database, including 21,522 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21522 hom., cov: 32)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 8 publications found

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.221+35654T>G		intron_variant	Intron 3 of 26	ENST00000531066.6	NP_001316559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.221+35654T>G		intron_variant	Intron 3 of 26	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79555 AN: 151894 Hom.: 21501 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79612 AN: 152012 Hom.: 21522 Cov.: 32 AF XY: 0.529 AC XY: 39337 AN XY: 74308

African (AFR) AF: 0.422 AC: 17482 AN: 41436

American (AMR) AF: 0.597 AC: 9118 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3466

East Asian (EAS) AF: 0.861 AC: 4453 AN: 5172

South Asian (SAS) AF: 0.739 AC: 3551 AN: 4802

European-Finnish (FIN) AF: 0.476 AC: 5044 AN: 10586

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36288 AN: 67948

Other (OTH) AF: 0.519 AC: 1098 AN: 2116

Alfa AF: 0.539 Hom.: 40485

Bravo AF: 0.526

Asia WGS AF: 0.753 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.4
DANN	Benign	0.77
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs713503; hg19: chr11-16999882;